N-(Methanesulfonyl)-16-phenoxyprostaglandincarboxamides: tissue-selective, uterine stimulants.
In an effort to develop tissue-selective prostaglandin analogues resistant to the metabolic inactivating pathways of the natural materials, hybrid compounds modified both at C-1 with a sulfonimide moiety and in the n-amylcarbinol side chain with substituted phenoxy groups were synthesized and evaluated in a variety of in vitro models. Several of these analogues exhibited potent, tissue-selective, uterine stimulant activity, a finding subsequently confirmed in clinical studies with one member of this series, N-(methanesulfonyl)-16-phenoxy-omega-tetranor-PGE2-carboxamide (CP-34089/ZK-57671, sulprostone).
D000020:Abortifacient Agents, Nonsteroidal / Q000138:chemical synthesis; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006168:Guinea Pigs; D000882:Haplorhini; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D009928:Organ Specificity; D011247:Pregnancy; D011465:Prostaglandins, Synthetic / Q000138:chemical synthesis* / Q000494:pharmacology; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects*
D000020:Abortifacient Agents, Nonsteroidal; D011465:Prostaglandins, Synthetic; D006911:Hydroxyprostaglandin Dehydrogenases